B-Cell Depleting Therapies: Fire-and-Forget or Treat-to-Target?

B-cell depleting therapies have become an increasingly popular choice for various glomerular diseases. However, given that the data on rituximab doses comes from a predominantly Western population, lower doses are frequently used in South and Southeast Asia. While it has been demonstrated that transient B-cell depletions can be achieved with low-dose rituximab, evidence suggest that clinical remissions require rapid, sustained, and ‘complete’ peripheral B-cell depletion (defined as a CD19 count of 0 cells/mm 3 ). Furthermore, depletion of tissue-resident B-cells and certain resistant B-cell subsets (plasmablasts, double-negative (DN) B-cells, and circulating memory B-cells) also correlates with better clinical remissions. Notably, obinutuzumab outperforms rituximab in this regard, possibly due to different pharmacodynamic actions mediated by direct B-cell cytotoxicity rather than complement-dependent cytotoxicity (CDC). Thus, though there is evidence that low-dose rituximab is sufficient to achieve desired clinical outcomes in a subset of patients, several additional factors should be considered while tailoring therapy to peripheral B-cell depletion.